PCDH8 and PCDH9 are both part of the protocadherin family of proteins, which are involved in cell-cell adhesion and communication in the brain. Research suggests that mutations or disruptions in these genes may play a significant role in the pathophysiology of autism and epilepsy. PCDH8, in particular, has been associated with alterations in synaptic function, which could contribute to the neurodevelopmental delays seen in autism spectrum disorder (ASD). Similarly, PCDH9 has been linked to neuronal excitability and synaptic stability, suggesting that its dysfunction may contribute to the seizure activity observed in epilepsy. Both genes appear to influence critical neuronal processes, with disruptions potentially leading to the altered brain connectivity and synaptic plasticity seen in these conditions.

Early epileptic seizures are thought to potentially exacerbate the severity of autism spectrum disorder (ASD) symptoms. Seizures occurring during critical periods of brain development may interfere with neurodevelopmental processes, leading to increased cognitive and behavioural impairments. The presence of epilepsy in early childhood is often associated with a higher risk of more severe autism symptoms, including language delays, social difficulties, and intellectual disability. Furthermore, the neural disruptions caused by seizures could contribute to atypical brain connectivity and sensory processing, amplifying the challenges faced by individuals with both autism and epilepsy.

Pcdhs are essential in adult neural stem cells (NSCs) as they regulate key processes like cell adhesion, migration, and differentiation. These functions are crucial for maintaining the balance between self-renewal and differentiation of NSCs, ensuring proper neurogenesis and tissue repair in the adult brain. In the context of brain cancer, dysregulation of Pcdhs can affect the stem-like properties of cancer cells, potentially contributing to tumour initiation and progression. Studying the role of Pcdhs in adult NSCs is critical for understanding both normal neural development and the mechanisms driving brain cancer, which could open doors to targeted therapies for neurological diseases and brain tumours.