KDM5C is an X-linked histone demethylase that specifically removes methyl groups from histone H3 lysine 4 (H3K4me2/3), playing a central role in transcriptional regulation 1. The enzyme demethylates trimethylated and dimethylated, but not monomethylated H3K4, and participates in transcriptional repression of neuronal genes by recruiting histone deacetylases and REST complexes at neuron-restrictive silencer elements 1. In neurodevelopment, KDM5C functions as a developmental safeguard controlling WNT signaling output to regulate the timely transition from primary to intermediate progenitor cells during neurogenesis 2. Disruption of this function leads to intellectual disability, with transient WNT pathway alterations sufficient to rescue cognitive deficits 2. In renal cell carcinoma, KDM5C mutations associate with altered angiogenesis and metabolic reprogramming 3. KDM5C regulates glucose-6-phosphate dehydrogenase and HIF-related genes, controlling glycogen metabolism and pentose phosphate pathway flux; loss of KDM5C increases ferroptosis resistance through enhanced NADPH/glutathione production 4. KDM5C is classified as a cancer driver tumor suppressor gene across multiple cancer types 5. Mutations in KDM5C occur in X-linked intellectual developmental disorder, Claes-Jensen type, and represent immunogenic targets in therapeutic neoantigen vaccination approaches 6.