Ferric-chelate reductase 1-like protein (FRRS1L)

Ferric-chelate reductase 1-like protein (FRRS1L) is a neuronal protein primarily expressed in the central nervous system, especially the hippocampus, cortex, and thalamus. FRRS1L is a component of the AMPA receptor (AMPAR) complex but does not function as a canonical AMPA receptor subunit. Rather, it participates in the early biogenesis and maturation of the AMPAR complex, interacting transiently with core AMPAR proteins (GluA1-GluA4/GRIA1-4) and facilitating glycosylation processes required for functional surface expression of these glutamate receptors. Loss or mutation of FRRS1L in humans causes a severe neurodevelopmental disorder termed developmental and epileptic encephalopathy 37 (DEE37/EIEE37), characterized by early-onset epilepsy, motor impairment, and intellectual disability, likely due to the dramatically reduced presence and function of AMPA receptors at excitatory synapses. Although not a classical drug target at present, its crucial role in excitatory neurotransmission and involvement in epilepsy make it a molecule of therapeutic interest, especially for AMPAR-targeted interventions.

Other names

DOMON domain-containing protein FRRS1Lbrain protein CG-6C9orf4CG-6CG6Developmental and epileptic encephalopathy 37 (DEE37)Early infantile epileptic encephalopathy 37 (EIEE37)