RUSC2 (RUN and SH3 domain containing 2) is a vesicular trafficking adaptor protein that functions in membrane transport at the trans-Golgi network (TGN) and cell periphery. RUSC2 associates with the AP-4 complex and serves as a direct effector of the Rab35 GTPase, with Arg1015 functioning as a "pseudo-arginine finger" to stabilize GTP-bound Rab35 1. The protein couples AP-4-dependent vesicles to kinesin-1 motors via interaction with kinesin light chains, facilitating peripheral distribution of ATG9A-containing vesicles and controlling basal EGFR cell surface display and recycling 23. RUSC2 depletion impairs EGFR transport from the Golgi and reduces EGF-induced cell proliferation, indicating physiologic importance for growth factor signaling 3. Genetically, loss-of-function mutations in RUSC2 cause autosomal recessive intellectual developmental disorder 61, characterized by central hypotonia, microcephaly, moderate-to-severe intellectual disability, early-onset epilepsy, and absent corpus callosum splenium 45. Emerging evidence suggests circular RNA derived from RUSC2 (circ_RUSC2) has disease-suppressive functions in cardiovascular and cancer contexts, though these involve the circular transcript rather than the protein product 67.