Functional characterization of the P1059L mutation in the inositol 1,4,5-trisphosphate receptor type 1 identified in a Japanese SCA15 family

► A Pro-1059-to-Leu substitution in the IP3 receptor type 1 (IP3R1) was recently identified in spinocerebellar ataxia type 15. ► The P1059L mutation of human IP3R1 enhanced IP3 binding affinity and decreased the cooperativity of IP3-induced Ca2+ release. ► The P1059L mutant, however, generated Ca2+ signals that were indistinguishable from wild-type IP3R1 in B lymphocytes. ► The P1059L mutation identified in a SCA15 family leaves the Ca2+ release activity of IP3R1 largely unaffected.