FKBP36 is an inherent multifunctional glyceraldehyde-3-phosphate dehydrogenase inhibitor.

FKBP36 has been previously shown to be a crucial factor in spermatogenesis because of its interplay with the synaptonemal complex protein SCPI. Here we show that beyond this function, FKBP36 forms complexes with glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12) and Hsp90. Both proteins bind independently to different sites of the FKBP36 tetratricopeptide repeat domain. The interaction between FKBP36 and GAPDH directly inhibits the catalytic activity of GAPDH. In addition, FKBP36 expression causes a significant reduction of the GAPDH level and activity in COS-7 cells. Particularly in the cytosolic fraction, GAPDH was depleted by FKBP36 expression. Thus, FKBP36 diminishes GAPDH activity by direct interaction and down-regulation of GAPDH, which represents a previously unknown mechanism of GAPDH regulation and a novel function of FKBP36 in testis-specific signaling.