CYS1 encodes cystin, a 158-amino acid protein localized to primary apical cilia of renal ductal epithelial cells 1. Cystin functions as a regulator of renal epithelial cell differentiation and cystogenesis through interaction with the tumor suppressor necdin, which modulates Myc proto-oncogene expression 2. The protein is expressed in the cytosol and cilium 1 and acts as a transcriptional target of the transcription factor TFAP2B, participating in a renal gene regulatory network alongside PKHD1 3. CYS1 mutations cause autosomal recessive polycystic kidney disease (ARPKD), a monogenically inherited disorder characterized by early-onset cyst development and progressive renal dysfunction 4. CYS1 represents a minor locus for ARPKD, with mutations identified in affected families 4. The cpk mouse model, harboring Cys1 mutations, demonstrates that loss of functional cystin leads to uncontrolled Myc expression, driving excessive renal tubular proliferation and cystic dilatation of distal tubules and collecting ducts 2. A human patient with homozygous CYS1 splicing mutations presented with ARPKD phenotype 2, confirming human disease relevance. Due to phenotypic and genetic overlap among PKD-causing genes, next-generation sequencing panels including CYS1 are recommended for clinical diagnostics 4.