GIGYF1 is a regulatory protein that functions as a coordinator of insulin-like growth factor 1 receptor (IGF-1R) signaling and translational control, with critical roles in neurodevelopment and cognitive function. Primary Function and Mechanism: GIGYF1 regulates IGF-1R recycling to the cell surface 1, enabling proper IGF-1R/ERK signaling pathway activation. Additionally, GIGYF1 represses mRNA translation initiation through a distinct mechanism: it binds eukaryotic translation initiation factor 3 (eIF3) subunits and disrupts their interaction with eIF4G1, causing transcript-specific translational repression 2. GIGYF1 also regulates VCP/p97 function during transcription stress responses 3. Disease Relevance: GIGYF1 disruption is strongly associated with autism spectrum disorder and related neurodevelopmental disorders 14. Heterozygous loss-of-function variants cause social impairments without significant cognitive deficits, while homozygous mutations produce more severe social and cognitive impairments accompanied by reduced upper-layer cortical neuron numbers 1. GIGYF1 variants also associate with type 2 diabetes 5, adult cognitive function 6, alcohol consumption patterns 7, and sleep disturbance 4. Clinical Significance: GIGYF1 haploinsufficiency impairs neurodevelopment through disrupted IGF-1R signaling 1, while GIGYF1 deficiency in excitatory neurons specifically recapitulates autism-relevant behavioral phenotypes 4, suggesting neuron-type-specific therapeutic targeting may be beneficial.