Dnajc5, also known as cysteine tandem protein (CSPα), is a member of the DnaJ/Hsp40 family of co-chaperones. It plays crucial roles in multiple biological processes, such as maintaining lysosomal homeostasis, regulating protein secretion, and synaptic function. It is involved in pathways like unconventional protein secretion, endosomal microautophagy, and is associated with neurodegenerative diseases and cancer [1,2,3].

In neurodegenerative diseases, mutations in Dnajc5 are associated with adult neuronal ceroid lipofuscinosis (ANCL), a dominant-inherited neurodegenerative disease. Dysfunction of Dnajc5-related processes, like misfolding-associated protein secretion (MAPS) and endosomal microautophagy, leads to lipofuscin accumulation and neurodegeneration. In Drosophila ANCL models, expressing ANCL-associated Dnajc5 mutants generates lipofuscin-like substances and induces neurodegeneration [3].

In cancer, Dnajc5 protein expression is highly detectable in human hepatocellular carcinoma (HCC) tissues. It promotes HCC cell proliferation by enhancing the degradation of p27 through interacting with SKP2 [2].

In conclusion, Dnajc5 is essential for maintaining normal cellular functions, especially in the context of protein quality control and synaptic stability. Model-based research, such as Drosophila ANCL models, has revealed its role in neurodegenerative diseases like ANCL. In addition, its oncogenic function in HCC shows its significance in cancer research, providing insights into potential disease mechanisms and therapeutic targets.