VPS13C, also known as PARK23, is a protein-coding gene. It encodes a lipid transfer protein that localizes to contact sites between the endoplasmic reticulum (ER) and late endosomes/lysosomes [2,3,6]. It plays a crucial role in regulating mitochondrial function through the endolysosomal pathway in neurons [1]. Mutations in VPS13C are associated with early-onset Parkinson's disease (PD) and dementia with Lewy bodies (DLB) [1].

Loss-of-function studies have provided key insights. Depleting VPS13C in HeLa cells causes lysosome accumulation with an altered lipid profile, activates the DNA-sensing cGAS-STING pathway due to elevated cytosolic mitochondrial DNA and defective activated STING degradation [2]. In human iPSC-derived dopaminergic neurons, loss of VPS13C disrupts lysosomal morphology, dynamics, motility, hydrolytic activity, and acidification, and decreases the phospho-Rab10-mediated lysosomal stress response [4]. Additionally, VPS13C deficiency in cervical cancer cells promotes cisplatin resistance by upregulating GSTP1 and inhibiting the JNK pathway [5].

In summary, VPS13C is essential for maintaining lysosomal and mitochondrial homeostasis. Studies on VPS13C, especially through loss-of-function models, have significantly enhanced our understanding of its role in PD and other diseases, such as cervical cancer's chemoresistance. These findings may help develop novel therapeutic strategies for related disorders.