Inborn errors of immunity (IEI), also known as primary immune deficiencies, are rare diseases caused by distinct pathogenic genetic variants, affecting approximately 1 in 25,000 people. While IEI are primarily associated with increased susceptibility to infection, autoimmunity, and cancer, recent clinical research indicates their impact extends to multiple systems, including the brain. Specifically, activated PI3K-Delta Syndrome (APDS), a rare genetic disorder resulting from mutations in the Pik3cd gene encoding the PI3Kδ enzyme, has been recently linked to neurodevelopmental disorders (NDD).Our current research focuses on understanding how alterations in the PI3Kδ pathway affect molecular functions and cognitive behavior. Previous studies from our lab have shown neurodevelopmental delay and sensorimotor deficits in APDS patients and in heterozygous Pik3cdtm1.1Klog mouse models. However, it remains unclear whether monozygotic mutations within Pik3cd lead to increased disease severity.Using heterozygous and homozygous Pik3cdtm1.1Klog knock-in mouse models, we investigated alterations in visual motor responses, locomotion, anxiety-like behavior, learning behaviors, and social interactions. We observed deficits in the eyeblink conditioning responses, a type of cerebellar-dependent sensorimotor learning, where mice learn to associate a conditional stimuli (visual cue) to an unconditional stimuli (air puff) resulting in a learned eye blink response, otherwise called a conditional response (CR). Our results suggest that PI3Kδ overactivity leads to sensorimotor learning deficits. This finding is in line with previous studies which show that mouse models for Autism Spectrum Disorder display sensorimotor integration deficits in paradigms such as eyeblink conditioning. Our future studies will explore the molecular mechanisms underpinning these observed NDD phenotypes.