GPRC5D is a G protein-coupled receptor involved in hard keratin expression and hair/nail development [UniProt]. In multiple myeloma, GPRC5D has emerged as a critical immunotherapy target due to its nearly ubiquitous expression on malignant plasma cells with limited expression on essential normal tissues 1. The protein is expressed on MM cell surfaces and serves as a target for T-cell-redirecting immunotherapies 2. Bispecific antibodies (BsAbs) simultaneously binding GPRC5D and CD3 recruit T cells to myeloma cells, inducing T-cell activation and tumor cell elimination 34. Talquetamab, a GPRC5D/CD3 BsAb, demonstrated 70% response rates in heavily pretreated patients with manageable toxicity profiles 4. CAR T-cell therapies targeting GPRC5D similarly show efficacy, including activity in BCMA-escape disease, with 71% overall response rates 5. Combination approaches with teclistamab achieved 80% response rates with durable responses at 18 months, though with increased infection rates 6. Resistance mechanisms include antigen downregulation and biallelic GPRC5D mutations arising during therapy, representing tumor-intrinsic escape mechanisms 7. Current clinical strategies include BsAbs, CAR T cells, and antibody-drug conjugates for relapsed/refractory MM 1.