GPRASP2 is an X-linked gene encoding a G protein-coupled receptor-associated sorting protein involved in regulating GPCR trafficking and stability. Its primary function involves controlling CXCR4 stability and cellular localization, critical for hematopoietic stem cell function and B-cell trafficking in germinal centers 12. GPRASP2 localizes to the cytoplasm and nucleus, binding GPCRs and interacting with trafficking machinery 3. Mechanistically, GPRASP2 participates in Hedgehog signaling through a Smoothened-GPRASP2-Pifo complex in primary cilia; GPRASP2 disruption downregulates key pathway components (Smo, Gli1, Gli2), triggering auditory cell apoptosis via mitochondrial damage 4. GPRASP2 is associated with X-linked deafness (SHL); mutations cause syndromic hearing loss with unique clinical features 5. The gene is also implicated in autism spectrum disorder, with genome-wide association identifying GPRASP2 among 17 X-linked ASD-associated genes 6. GPRASP2 deficiency in mice triggers B-cell lymphoproliferative disease resembling human aggressive lymphomas through aberrant GC accumulation and excessive somatic hypermutation 1. Expression patterns during early zebrafish development show enrichment in nervous system and otic structures, supporting its neurodevelopmental roles 7. Clinical significance includes potential therapeutic targets for enhancing hematopoietic transplantation and treating hedgehog-dependent cancers.