Ap1g1, encoding gamma-1 subunit of adaptor-related protein complex 1 (AP1γ1), is crucial for the formation of clathrin-coated intracellular vesicles, mediating selective intracellular vesicular trafficking and polarized localization of somatodendritic proteins in neurons [1,2,3]. The AP1γ1-mediated adaptor complex functions at the trans-Golgi network and endosomes, and is ubiquitously expressed in eukaryotic cells [2,3]. Zebrafish and mouse models have been valuable in studying its functions [2,3].

In zebrafish, knocking out ap1g1 leads to severe morphological defect and lethality at the blastula stage. Heterozygous zebrafish show reduced fertility and morphological alterations in the brain, gonads and intestinal epithelium, with dysregulated cadherin-mediated cell adhesion [2]. In mice, a hypomorphic mutation of Ap1g1 causes abnormalities in sensory epithelial cells of the inner ear, pigmented epithelial cells of the retina, follicular epithelial cells of the thyroid gland, and the germinal epithelium of the testis [3]. In humans, de novo and bi-allelic variants in AP1G1 are associated with a neurodevelopmental disorder characterized by mild to severe intellectual disability, epilepsy, and developmental delay [1].

In conclusion, Ap1g1 is essential for normal development and function in various organisms. Studies using gene-knockout models in zebrafish and mice have revealed its role in processes such as neurodevelopment, fertility, and cell adhesion, and its association with human neurodevelopmental disorders. These models provide valuable insights into the functions of Ap1g1 and potential implications for understanding related diseases.