GPRASP1 is a critical regulator of G-protein coupled receptor (GPCR) trafficking and degradation that modulates cellular signaling through lysosomal sorting mechanisms. The protein primarily functions by promoting GPCR degradation through its interaction with BECN2 and the endosomal sorting machinery 1. GPRASP1 facilitates K63-linked ubiquitination of target GPCRs like GPR4 and CXCR4, enhancing their binding to RABGEF1 to activate RAB5 for endosomal conversion and subsequent packaging into multivesicular bodies for lysosomal degradation 2. Loss of GPRASP1 function has significant disease implications across multiple systems. In vascular biology, GPRASP1 variants cause arteriovenous malformations by preventing GPR4 degradation, leading to aberrant GPR4/cAMP/MAPK signaling and endothelial dysfunction 2. In hematopoiesis, GPRASP1 deficiency improves hematopoietic stem cell transplantation outcomes by stabilizing CXCR4, enhancing cell survival and niche retention 3, but paradoxically increases lymphoproliferative disease risk through disrupted B-cell differentiation and excessive somatic hypermutation 4. Clinically, GPRASP1 shows promise as a biomarker in cancers, where reduced expression correlates with better prognosis and enhanced immune infiltration in head and neck and pancreatic cancers 56. Additionally, GPRASP1 deletion prevents adverse effects of chrX β2-adrenoceptor stimulation, suggesting therapeutic potential in respiratory diseases 7.