<p dir="ltr">With growing environmental concerns and stricter regulations on high global warming potential (GWP) refrigerants, as well as the potential ban on per- and polyfluoroalkyl substances (PFAS), the quest for sustainable alternatives has intensified. Due to its low GWP and excellent properties, propane (R290) is considered a promising long-term solution for space conditioning and water heating. However, safety concerns surrounding its flammability have hindered its widespread adoption in residential settings.</p><p dir="ltr">This work adopts a critical review framework to evaluate recent advancements in residential heat pump and air conditioning systems utilizing R290 as a refrigerant, offering deeper insights to enhance our understanding of these technologies. It includes aspects such as thermophysical properties, system design and performance, current regulations, and safety concerns. The research examines the key advantages of R290 that contribute to its superior system performance and summarizes best design practices. It also addresses challenges, such as reducing the refrigerant charge to meet safety standards requirements. Studies have demonstrated that a specific charge of as low as 30 g/kW is attainable. These insights were then used to assess the feasibility of implementing R290 in various residential systems. This study suggests that employing R290 in small-sized systems such as mini-split and window air conditioners should not pose significant challenges. However, its adaptation into larger unitary systems remains uncertain, prompting the need for further safety assessments and potential updates to safety standards. Furthermore, this review provides a summary of existing research gaps in the current literature and future research directions.</p><p dir="ltr">Although R290 offers long-term potential as a low-GWP refrigerant, its application is limited by two key drawbacks: high flammability and low volumetric capacity. One way to address these limitations is by blending R290 with refrigerants that either reduce flammability or enhance volumetric capacity. To explore this approach, the study conducts a theoretical screening of R290 refrigerant mixtures to identify drop-in replacements for R410A in heat pumps and air conditioners. Binary and ternary R290 blends were systematically evaluated using 10 pure refrigerants, which included hydrocarbons (HC), hydrofluorocarbons (HFC), hydrofluoroolefins (HFO), and CO<sub>2</sub>. The mixtures were investigated in 0.04-mole fraction increments, optimizing thermodynamic performance, environmental impact, and flammability characteristics. The most promising candidates are blends that primarily consist of HFOs mixed with R290. Despite their potential, all identified mixtures exhibit trade-offs or limitations that affect their overall applicability. This work highlights the potential of carefully engineered refrigerant blends to achieve regulatory compliance while meeting operational performance requirements.</p><p dir="ltr">In light of flammability-related constraints, which often require the use of less efficient indirect systems, this study explores advanced cycle architectures for enabling the efficient utilization of R290 within residential buildings. This study develops and experimentally evaluates a novel two-stage, variable-speed, liquid-to-liquid heat pump with R290 refrigerant for cold climates. Unlike prior studies, it introduces independent speed control of the low- and high-stage compressors, providing the first experimental dataset for R290 in two-stage systems. The system achieved an 18.3% increase in heating capacity and a 5.8% improvement in the coefficient of performance (COP) at an ambient temperature of -8.3 °C in two-stage mode compared to single-stage operation, although with an 11% increase in refrigerant charge level. The study also highlights the critical role of the secondary fluid in system design, overall performance, and thermal comfort. Specifically, a design mismatch was identified between hydrocarbon refrigerants and aqueous secondary fluids in the evaporators of indirect systems operating at low evaporation temperatures. These findings offer essential guidance for designing high-performance, regulation-compliant heat pumps suitable for safe residential use in cold climates.</p><p dir="ltr">Finally, the study presents the development and validation of a high-fidelity dynamic model for the R290 two-stage heat pump system using Modelica. An optimized control strategy was implemented to regulate two compressor speeds and two expansion valves, resulting in a system capable of meeting the rated capacity of 5.5 kW down to -20 °C with a COP exceeding 2.0 at an ambient temperature of -15 °C. Refrigerant charge analysis revealed that approximately 65% of the total 1.0 kg charge is either dissolved in oil or stored in the high-stage suction accumulator. This result points to significant opportunities for charge reduction and system optimization, reinforcing the viability of R290 as a safe and efficient low-GWP refrigerant for residential applications.</p>