GPATCH2L is a nuclear protein containing a G-patch domain with roles in multiple disease pathways. Its primary function remains incompletely characterized, though it localizes to the nucleus and mediates protein interactions 1. In systemic sclerosis, GPATCH2L shows increased tubular expression in scleroderma renal crisis (SRC) kidney tissue compared to controls 1, and genetic variants in GPATCH2L (rs935332) associate with SRC development in anti-RNA polymerase III antibody-positive patients across two independent cohorts 1. Functionally, GPATCH2L demonstrates relevance to Parkinson's disease susceptibility; RNAi-mediated knockdown studies revealed it modulates mitochondrial dynamics in human neuronal cultures and shows evidence of genetic replication in independent datasets 2. Additionally, GPATCH2L variants nominally associate with orofacial cleft risk in parent-of-origin effects under conditions of inadequate periconceptional folic acid supplementation 3. Recent genome-wide association studies identify GPATCH2L as a prioritized causal gene for pilonidal sinus disease, suggesting involvement in hair growth and patterning pathways 4. Overall, GPATCH2L contributes to pathogenesis in vascular, neurological, developmental, and dermatological diseases, primarily through effects on tissue-specific cellular processes.