Aryl-hydrocarbon-interacting protein-like 1 (AIPL1)

Aryl-hydrocarbon-interacting protein-like 1 (AIPL1) is a specialized co-chaperone protein expressed almost exclusively in retinal photoreceptor cells and the pineal gland, where it functions with HSP90 to promote the folding, stabilization, and maturation of cGMP-specific phosphodiesterase-6 (PDE6)[2][3][5]. It contains an FKBP-like domain and a tetratricopeptide repeat (TPR) domain, enabling it to bind both HSP90 and PDE6 subunits, and potentially facilitate conformational changes necessary for PDE6 activity[2]. AIPL1 is essential for maintaining appropriate levels and assembly of PDE6; its absence or mutation causes rapid photoreceptor degeneration and severe congenital blindness, as seen in Leber congenital amaurosis type 4 (LCA4)[1][3][5]. No approved drugs currently target AIPL1, though gene therapy approaches are under investigation. Its interactions with HSP90 are structurally unique among co-chaperones, and disruption of these interactions leads to disease[2].

Other names

AIPL1AIPL2LCA4aryl hydrocarbon receptor interacting protein like 1aryl-hydrocarbon-interacting protein-like 1

Restoration of AIPL1 function via gene therapy to rescue PDE6 folding/maturation. Hypothetical: Small molecule mimetics targeting AIPL1 interface with NUB1 or HSP90 to modulate its chaperone activity, not yet clinically realized.