Psap, also known as presenilin-associated protein, is a gene with diverse functions. It encodes prosaposin, which is involved in glycosphingolipid metabolism [2,3]. Prosaposin can be cleaved into four saposins, such as saposin C which acts as a co-activator of glucocerebrosidase [2,4]. It is also associated with lysosomal function and lipid homeostasis [1,3]. Genetic models, like KO/CKO mouse models, can be valuable in studying its functions.

In dopaminergic PSAP-deficient (cPSAPDAT) mice, there is hypolocomotion, depression/anxiety-like symptoms, and impaired dopaminergic neurotransmission. Spatial lipidomics shows an abnormal lipid profile in their brains, with accumulation of certain lipids and reduction of sphingolipids. Overexpression of PSAP via AAV and encapsulated cell biodelivery protects against 6-OHDA and α-synuclein toxicity in wild-type rodents, suggesting PSAP's role in maintaining dopaminergic lipid homeostasis and counteracting experimental parkinsonism [3].

In conclusion, Psap is crucial for maintaining lipid homeostasis, especially in dopamine neurons. Studies using cPSAPDAT mouse models have revealed its significance in Parkinson's-related phenotypes, providing insights into the role of Psap in neurodegenerative diseases [3].