G protein-coupled receptor class C group 5 member D (GPRC5D) is an orphan GPCR belonging to the RAIG1 family. The GPRC5D gene is located on chromosome 12p13.3, encoding a 345-amino acid protein with a seven-transmembrane domain . Its expression in normal adult human tissues is restricted primarily to plasma cells and hard-keratinized structures including hair follicles, nails, and lingual filiform papillae . Importantly, GPRC5D is highly and specifically expressed on malignant plasma cells in multiple myeloma (MM), with minimal expression on essential normal tissues . Elevated GPRC5D expression correlates with poor prognosis in MM patients . Although its endogenous ligand and physiological function remain elusive, GPRC5D has emerged as a promising immunotherapeutic target for MM, particularly for patients relapsed/refractory to BCMA-targeted therapies . Several GPRC5D-targeted modalities are under development, including the bispecific antibody talquetamab (the only FDA-approved GPRC5D-targeted therapy), chimeric antigen receptor (CAR) T cells, and antibody-drug conjugates (ADCs) . Ongoing research focuses on overcoming antigen escape mechanisms and managing on-target toxicities involving skin, nails, oral mucosa, and rare cerebellar events.