The Kidins220 (Kinase D-interacting substrate of 220 kDa) or ARMS (Ankyrin repeat-rich membrane-spanning) protein was originally identified as a substrate for protein kinase D (PKD) in neural cells. Kidins220 is a member of the Kidins220/ARMS and PifA (KAP) family of P-loop nucleotide phosphatases (NTPases).

Kidins220 is an integral membrane protein, containing four transmembrane segments in the central part of the molecule, and N- and C-terminal tails both exposed to the cytoplasm. Kidins220 possesses numerous domains that mediate protein–protein interactions. The N-terminus of Kidins220 contains eleven ankyrin repeats which form a concave binding surface that is accessible to molecular partners. Kidins220 contains Walker A and Walker B (involved in the binding of nucleotides) motifs in its juxta-membrane regions flanking the N- and C-termini. The C-terminus of Kidins220 includes several protein–protein interaction domains that are involved in inter- and intra-molecular interactions. The last four amino acids of Kidins220 constitute a PDZ-binding motif that binds the PDZ domain of α-syntrophin, thereby forming a complex that is associated with the EphA4 receptor at the neuromuscular junction¹.

Neurotrophin signaling is responsible for a wide variety of neuronal functions and is dependent upon two different transmembrane receptor types; the Trk receptor tyrosine kinase and the p75 neurotrophin receptor that belongs to the TNF receptor family. Kidins220 interacts with TrkA, TrkB, TrkC receptors, and with p75^NTR. Kidinis220 is rapidly tyrosine phosphorylated after binding of neurotrophins to Trk receptors and provides a docking site for the CrkL–C3G complex, resulting in Rap1-dependent sustained ERK activation².

Kidins220 also associates with NMDA receptors. Upon overstimulation of the NMDA receptor, activity-dependent Ca²⁺ influx through NMDA receptors leads to a decrease in Kidins220 levels owing to transcriptional downregulation and protein cleavage by calpain¹.