Fenretinide binding to the lysosomal protein saposin D alters ceramide solubilization and hydrolysis.

Fenretinide is a synthetic retinoid pharmaceutical linked to ceramide build-up in vivo. Saposin D is an intralysosomal protein necessary for ceramide binding/degradation. We show, via electronic absorption spectroscopy, fluorescence spectroscopy, and ceramide hydrolysis assays, that fenretinide is bound by saposin D {K a = (1.45 ± 0.49) × 105 M-1}, and affects ceramide solubilization/degradation.