Abca13, a member of the ATP-binding cassette subfamily A, is predicted to be the largest ABC protein, consisting of 5058 amino acids with a long N-terminal region [1,3]. It is involved in cholesterol trafficking, accelerating cholesterol internalization by endocytic retrograde transport in neurons [1].

In Abca13 KO mice, deficits of prepulse inhibition were observed. Vesicular cholesterol accumulation and synaptic vesicle endocytosis were impaired in primary cultures of Abca13 KO cortical neurons. Also, mutations in the ABCA13 gene associated with psychiatric disorders disrupted the protein's subcellular localization and impaired cholesterol trafficking, suggesting its link to the pathophysiology of psychiatric disorders [1]. In a monkey model of autism with ABCA13 deletion, the neuronal formation in the cortex was disorganized, and the catecholaminergic, GABAergic, and serotoninergic neuronal systems were impaired, indicating its role in neurodevelopment [2].

In conclusion, Abca13 plays a crucial role in cholesterol trafficking in neurons, and its dysfunction is associated with psychiatric and neurodevelopmental disorders. The use of gene knockout models, such as Abca13 KO mice and the ABCA13-deleted monkey model, has been instrumental in revealing these functions and disease associations, providing insights into the pathophysiology of related disorders.