GIMAP5 is a GTPase primarily expressed in lymphocytes and endothelial cells that regulates immune cell survival and tissue homeostasis. In T lymphocytes, GIMAP5 controls cell survival by inhibiting GSK3A, thereby impairing GSK3A-dependent transcriptional programs and DNA damage responses during T cell proliferation 1. GIMAP5 restricts pathological accumulation of long-chain ceramides by interacting with protein kinase CK2 to attenuate ceramide synthase activation, a mechanism critical for preventing cell senescence and maintaining lymphocyte function 2. GIMAP5 operates within a protein complex with MFSD1 and GLMP to maintain lymphocyte development and suppress extramedullary hematopoiesis 3. In hepatic tissue, GIMAP5 is essential for maintaining liver sinusoidal endothelial cell (LSEC) specification and prevents capillarization; its loss causes portal hypertension 4. Additionally, GIMAP5 promotes respiratory syncytial virus degradation through interaction with mannose-6-phosphate receptor 5. Clinically, GIMAP5 deficiency causes early-onset lymphopenia, liver dysfunction, and portal hypertension 42. Genetic variants in GIMAP5 increase susceptibility to systemic lupus erythematosus and inflammatory bowel disease 67. Rare variants in GIMAP5 are associated with altered HbA1c response to metformin 8.