IgSFCAMs

IgSFCAMs, short for immunoglobulin superfamily cell adhesion molecules, constitute a large and diverse group of cell-surface proteins that belong to the immunoglobulin superfamily. They mediate cell–cell adhesion and transduce signals that regulate cell positioning, migration, and differentiation in development and tissue homeostasis. IgSFCAM interactions are often multivalent, enabling both homophilic and heterophilic binding, and can influence synapse formation in the nervous system as well as leukocyte trafficking in the immune system.

Most IgSFCAMs are single-pass type I transmembrane proteins. Their extracellular region typically contains one to several immunoglobulin-like (Ig) domains arranged in tandem, followed by one or more fibronectin type III–like segments in some families. The cytoplasmic tail often contains motifs that recruit cytoskeletal adapters and signaling molecules, allowing outside-in signaling.

Prominent members include ICAMs, VCAMs, NCAMs, and L1 family members. These molecules participate in neuronal development, axon guidance, synaptic maintenance, lymphocyte adhesion, and immune surveillance. They are also implicated in pathological processes such as tumor cell invasion and inflammatory diseases, where altered expression or adhesion properties can affect tissue permeability and cell migration.

Classification within IgSFCAMs is based on sequence similarity, domain organization, and functional interactions. Ongoing research explores their roles in nervous system connectivity, immune regulation, and their potential as therapeutic targets in autoimmunity and cancer.