Ctsd, also known as cathepsin D, is a lysosomal aspartic protease. It plays a vital role in maintaining cellular homeostasis, especially in neurons where it regulates the proteolytic activity of lysosomes. It is involved in pathways like autophagy and lysosomal function, and its dysregulation is linked to various neurodegenerative diseases [2,3]. Genetic models, such as gene knockout (KO) mouse models, have been crucial in studying its functions.

In ctsd-deficient mouse models, there is an accumulation of insoluble SNCA conformers in the brain, indicating that Ctsd is critical for SNCA/α-synuclein clearance, which is relevant to Parkinson disease (PD) [1]. In stroke models, a decrease in Ctsd protein levels and activity was observed in the mouse brain after stroke, along with lysosomal dysfunction. ShRNA-mediated knockdown of Ctsd in neurons further aggravated lysosomal dysfunction and cell death, suggesting that Ctsd-dependent lysosomal function is crucial for neuronal survival in cerebral ischemia [2].

In conclusion, Ctsd is essential for maintaining lysosomal function and proteolytic regulation in cells. Studies using KO mouse models have revealed its significance in neurodegenerative diseases like PD and in stroke-related neuronal survival. Understanding Ctsd's functions provides potential therapeutic approaches for these disease areas.