RFPL1 (ret finger protein-like 1) is a primate-specific gene on chromosome 22 that functions as a negative regulator of cell-cycle progression through G2/M phase transition 1. The protein localizes to the cytoplasm and contains a tripartite RING finger-coiled-coil-B30.2 domain structure characteristic of RING-B30 family proteins 2. RFPL1 executes its cell-cycle inhibitory function by promoting proteasomal degradation of cyclin B1 and CDK1 (Cdc2), preventing their accumulation during interphase and delaying mitotic entry 1. This activity is regulated by kinase-dependent mechanisms, with PKC activating and Cdc2 inhibiting RFPL1 1. Beyond cell-cycle control, RFPL1 expression is enriched during neural differentiation and early embryonic development 34. Evolutionary analysis reveals RFPL1,2,3 genes emerged and duplicated specifically in primates and higher primates, with positive selection and neofunctionalization events suggesting roles in primate neocortex development 3. Clinically, rare loss-of-function variants in RFPL1 showed significant segregation in familial severe chr22 obstructive pulmonary disease (COPD), though findings did not replicate in case-control studies 5. The gene's expression during cell differentiation and its anti-proliferative effects implicate RFPL1 in developmental processes requiring controlled cell-cycle lengthening.