From Genetics to Function: the Role of ABCA12 in Autism Neurobiology

ASD is a complex neurodevelopmental disorder with genetic, environmental, and molecular roots. Among the thousands of genes that have been associated with ASD, one critical factor has emerged as ABCA12, which plays an important role in lipid transport and metabolism. Traditionally, it has been related to skin disorders but has only recently been implicated in broader brain development and function. Some of the implicated effects include dysregulated lipid homeostasis, neuroinflammation, oxidative stress, and abnormalities in synaptic when the ABCA12 system is dysregulated. All the above processes are related to pathology in ASD. In this review, the emerging function of ABCA12 in autism neurobiology has been discussed; the core base is derived from in vivo models and preclinical studies. In vivo models such as mice and zebrafish that, in the previous studies had earlier shown impairments of ABCA12 which results in social deficiency behaviors but also perform repetitive actions. Based on the effects of the gene on molecular pathways, including neuronal signalling and membrane integrity, and identifying therapeutic approaches targeting ABCA12 or its downstream effects, preclinical studies have contributed to the integration of genetic, functional, and therapeutic perspectives for understanding the contribution of ABCA12 to ASD. These findings may unlock further investigations geared toward unravelling how lipid metabolism intricately influences neurodevelopment with regards to interventions available for use in ASD.

Graphical Abstract