Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22)

Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) is a neural-selective, transmembrane protein of the ADAM (a disintegrin and metalloprotease) family[2][4]. Unlike most ADAMs, ADAM22 lacks metalloprotease activity and acts mainly as a postsynaptic receptor for secreted LGI1 proteins, regulating the maturation, maintenance, and function of excitatory synapses in the central nervous system[2][3][1]. Through interactions with LGI1 and PDZ-scaffold proteins like PSD-95, ADAM22 organizes postsynaptic protein complexes and stabilizes AMPA receptor clusters, modulating synaptic strength and plasticity[3]. In the peripheral nervous system, it is crucial for Schwann cell differentiation and proper myelination[2]. Mutations in ADAM22 are associated with early infantile epileptic encephalopathy (EIEE61) and developmental and epileptic encephalopathy (DEE61)[4], and dysregulation has been implicated in tumor progression and endocrine resistance in breast cancer[2]. ADAM22 is also part of axonal Kv1 channel complexes, contributing to nerve conduction domain specialization[2].

Other names

ADAM metallopeptidase domain 22MDC2EIEE61DEE61Metalloproteinase-disintegrin ADAM22-3Metalloproteinase-like, disintegrin-like, and cysteine-rich protein 2