ZMIZ1 encodes a zinc finger transcriptional coactivator that regulates multiple signaling pathways critical for development and immune function. As a member of the PIAS protein family, ZMIZ1 enhances transcriptional activity through sumoylation-dependent mechanisms, particularly for the androgen receptor and NOTCH1 target genes including MYC 1. ZMIZ1 also functions as a coactivator in TGF-β signaling by increasing SMAD3/SMAD4 complex activity and regulates pyramidal neuron positioning during cerebral cortex development 1. In lymphatic endothelial cells, ZMIZ1 modulates Prox1 expression through chr10 remodeling, controlling proliferation, migration, and valve formation 2. During intrahepatic cholangiocarcinoma progression, ZMIZ1 acts as a core transcription factor in stress-responding tumor cells, with Zmiz1 knockout blocking disease initiation 3. Pathogenic ZMIZ1 variants cause neurodevelopmental disorder with dysmorphic facies and distal skeletal anomalies (NEDDFSA), characterized by intellectual disability, growth failure, microcephaly, and facial dysmorphism 1. In vivo, mutant ZMIZ1 alleles impair pyramidal neuron morphology and positioning 1. Additionally, ZMIZ1 variants associate with increased IgA nephropathy risk and celiac disease susceptibility across multiple populations 45. Some ZMIZ1-related neurodevelopmental disorders demonstrate incomplete penetrance 6.