REN encodes renin, a highly specific aspartic-type endopeptidase that initiates the renin-angiotensin system by cleaving angiotensinogen to generate angiotensin I, thereby regulating blood pressure and sodium retention 1. Renin is secreted from juxtaglomerular cells and functions in the extracellular space and plasma to orchestrate this proteolytic cascade 2. Beyond its classical endocrine role, renin also functions as a tumor suppressor; REN/KCTD11 serves as a substrate receptor of the Cullin3-RING ubiquitin ligase complex (CRL3REN), mediating polyubiquitylation and degradation of oncogenic proteins, with loss of REN occurring in approximately 30% of Sonic Hedgehog-dependent medulloblastomas 3. Mutations in REN cause autosomal dominant tubulointerstitial kidney disease (ADTKD-REN), characterized by progressive renal dysfunction with tubular atrophy and interstitial fibrosis 4. Affected patients present with distinctive signs of hyporeninemia including mild hypotension, mild hyperkalemia, childhood anemia, hyperuricemia, and gout in teenage years, with a median age at end-stage renal disease of approximately 45 years 2. Genetic testing rather than kidney biopsy is recommended for diagnosis of REN-related disease 2.