GPR149 is an orphan G protein-coupled receptor located on chromosome 3 with predicted neuropeptide binding and signaling capacity based on sequence homology [GO Annotations]. Its biological function remains largely uncharacterized, though emerging evidence suggests relevance in multiple disease contexts. GPR149 was identified as part of a locus (GPR149/MME) associated with venous thromboembolism (VTE) recurrence in a large genome-wide association study of 6,355 patients, highlighting a potential role in coagulation and thrombotic risk 1. In cancer biology, GPR149 hypermethylation serves as an independent prognostic marker in clear cell renal cell carcinoma, with hypermethylation significantly predicting shorter time-to-progression (hazard ratio 7.07, p<0.001) 2. Similarly, GPR149 methylation changes are observed in prostate cancer specimens, where it was identified among genes with altered methylation states in malignant tissue 3. Additionally, GPR149 expression is altered by FUS mutations associated with amyotrophic lateral sclerosis in iPSC-derived motor neurons, suggesting involvement in neurodegeneration pathways 4. These findings indicate GPR149 functions in thrombotic, neoplastic, and neurodegenerative processes, though its precise molecular mechanism as an orphan receptor requires further investigation.