Abelson helper integration site 1 protein (AHI1)

Abelson helper integration site 1 protein (AHI1) is a cytoplasmic, scaffolding protein that plays an essential role in human brain development, particularly in the cerebellum and cortex[2][5]. It encodes jouberin, a protein with multiple WD40 repeats and an SH3 domain, enabling interaction with proteins involved in intracellular trafficking, microtubule-dependent transport, and receptor endocytosis[1]. AHI1 forms complexes with HAP1 and is part of the basal body protein complex at the base of cilia[3]. Mutations in AHI1 lead to Joubert syndrome, marked by congenital brain malformations including mental retardation, and have been linked to increased risk of schizophrenia and autism[1][2]. Experimental deficiency of AHI1, especially in neuronal cells, impairs TrkB receptor signaling and can induce depressive-like behavioral changes in mice[1]. Although not a direct drug target, AHI1's pathway is closely related to neurotrophic factor signaling and emotional regulation, making it of therapeutic interest in neurodevelopmental and neuropsychiatric disease[1][2].

Other names

JouberinJBTS3ORF1FLJ20069dJ71N10.1AHI-1abelson helper integration site 1 protein homolog

AHI1 is not directly targeted by drugs, but its loss can be compensated by agents that enhance TrkB signaling (e.g., antidepressants), or by genetic overexpression of TrkB, resulting in normalization of depressive phenotypes[1].