Clathrin heavy chain 1

Clathrin Heavy Chain 1 (CLTC)

Clathrin heavy chain 1 is the primary structural protein of coated pits and vesicles, forming the polyhedral lattice that mediates clathrin-dependent endocytosis via interaction with adapter proteins at the plasma membrane and trans-Golgi network (UniProt: Q00610). Beyond vesicular transport, it participates in kinetochore fiber stabilization as part of the TACC3/ch-TOG/clathrin complex during mitosis, and contributes to early autophagosome formation through DNAJC6-mediated HSPA8 recruitment and lattice uncoating (UniProt: Q00610).

The protein is associated with autosomal dominant intellectual developmental disorder 56 (MRD56; MIM 617854), indicating its importance in neurodevelopmental function (UniProt: Q00610). Its roles in endosomal trafficking and autophagy are relevant to multiple cellular pathways implicated in neuronal homeostasis.

In Alzheimer's disease, clathrin heavy chain 1 shows an ambiguous direction of regulation across subcellular fractions in post-mortem AD brain compared to age-matched controls, with a mean log2 fold-change of −0.19 (Chaparral AD proteomics). This modest average decrease masks heterogeneous changes across the two fractions analyzed, suggesting complex compartment-specific alterations in clathrin-mediated trafficking or autophagy in AD pathology.