CHC22

CHC22, or clathrin heavy chain 22, is a vertebrate-specific isoform of the clathrin heavy chain family. It is encoded by the CLTCL1 gene in humans and represents a paralog of the ubiquitously expressed CHC17 (CLTC). As a clathrin heavy chain, CHC22 participates in forming clathrin-coated vesicles, but it functions in a distinct trafficking pathway that differs from classical endocytosis.

CHC22 expression is enriched in skeletal muscle and brain, with detectable but lower levels in adipose tissue and other organs. The protein localizes to intracellular membrane compartments and is associated with vesicle formation involved in intracellular sorting rather than plasma membrane vesicle dynamics typical of CHC17.

Functional studies indicate that CHC22 participates in trafficking at the trans-Golgi network and endosomal system, contributing to the biogenesis of GLUT4 storage vesicles in insulin-responsive tissues. This CHC22-dependent pathway supports the retention and regulated release of GLUT4, which is essential for insulin-stimulated glucose uptake. The CHC22 pathway is thought to operate largely separately from the canonical clathrin-mediated endocytosis driven by CHC17.

CHC22 forms clathrin coats by assembling into triskelions with light chains and interacts with adaptor proteins that help select cargo and shape membranes. Its trafficking role is characterized by membrane sorting and storage vesicle formation rather than rapid plasma membrane internalization.

Clinical and research relevance centers on glucose homeostasis and metabolic disease. Disruption of CHC22–dependent trafficking in model systems can impair insulin sensitivity and glucose handling, highlighting CHC22’s potential involvement in insulin resistance. In humans, ongoing studies examine genetic and expression variations for links to metabolic traits, though definitive clinical associations remain under investigation. CHC22 thus represents a specialized clathrin-coated machinery important for intracellular sorting and insulin-responsive glucose regulation.