SRCAP encodes a chr16 remodeler and transcriptional coactivator that catalyzes ATP-dependent exchange of histone H2A.Z/H2B dimers within nucleosomes, regulating gene expression through chr16 remodeling. It functions as a coactivator for CREB-mediated, steroid receptor-mediated, and Notch-dependent transcription. Pathogenic variants in SRCAP cause distinct neurodevelopmental phenotypes depending on variant location. Truncating variants in exons 33 and 34 cause Floating-Harbor syndrome, characterized by short stature, speech delay, and facial dysmorphism 1. Truncating variants outside this locus cause non-FLHS SRCAP-related neurodevelopmental disorder, featuring developmental delay, intellectual disability, behavioral problems, hypotonia, and musculoskeletal issues, with a distinct DNA methylation signature from Floating-Harbor syndrome 2. De novo SRCAP variants have been identified in individuals with syndromic intellectual disability 3. Beyond germline disease, somatic SRCAP mutations drive clonal hematopoiesis through altered H2A.Z deposition and DNA repair dysregulation, conferring selective advantage in hematopoietic stem cells 4. At the population level, SRCAP mutations show positive selection in clonal hematopoiesis and correlate with increased infection, death, and hematological malignancy risk 5. In cancer, SRCAP complex promotes lung adenocarcinoma progression by facilitating H2A.Z deposition at YAP/TAZ target promoters, with elevated SRCAP expression correlating with poor survival in non-small cell lung cancer patients 6.