Dnajc5-flox Mouse

Dnajc5, also known as cysteine tandem protein (CSPα), is a member of the DnaJ/Hsp40 family of co-chaperones. It is crucial for maintaining normal nerve tissue function. Palmitoylated Dnajc5 anchors on the membrane and is involved in unconventional protein secretion pathways, such as facilitating the secretion of α-synuclein [1]. It also safeguards lysosomal homeostasis through unconventional protein secretion and endosomal microautophagy, processes relevant to maintaining cellular health [2].

Mutations in Dnajc5 are associated with adult neuronal ceroid lipofuscinosis (ANCL), a neurodegenerative disease. In ANCL, abnormal triaging of misfolded proteins by Dnajc5 mutants causes lipofuscin accumulation. Uncoupling the two chaperoning activities of Dnajc5, which regulate lysosomal homeostasis, generates lipofuscin-like materials and induces neurodegeneration in a Drosophila ANCL model [3].

In conclusion, Dnajc5 is essential for maintaining lysosomal homeostasis and proper protein secretion, especially in nerve tissues. The study of Dnajc5 in genetic models like the Drosophila ANCL model has revealed its role in neurodegenerative diseases such as ANCL, providing insights into the underlying pathological mechanisms.