Regenerating the Senses: Stem Cell‐Derived Sensory Neurons and Functional Genomics in Neurological Disorders

ABSTRACT Sensory neuron disorders, such as peripheral neuropathies and trigeminal neuralgia, cause chronic pain and sensory dysfunction; however, regenerative treatments are limited. Human pluripotent stem cells (hPSCs) provide a powerful platform to model these diseases by generating functional sensory neuron subtypes, including nociceptors and mechanoreceptors. These hPSC‐derived neurons mimic key features of dorsal root ganglia (DRG), enabling the study of disease mechanisms and therapeutic responses in a human‐relevant system. When combined with functional genomics—such as CRISPR screens, single‐cell RNA‐seq, and epigenomic profiling—these models allow for the discovery of pathogenic pathways and drug targets. Patient‐specific iPSC‐derived neurons also support personalized medicine approaches. Brain organoids and animal models complement these systems by offering broader developmental insights and enabling in vivo validation. However, challenges remain in achieving full maturation, subtype specificity, and functional integration of hPSC‐derived neurons. Ethical and safety considerations with gene editing also persist. Continued advances in differentiation protocols, multi‐model integration, and collaborative efforts are key to unlocking the full therapeutic potential of stem cell‐derived sensory neurons. This perspective highlights recent progress in disease modeling and treatment strategies using hPSC‐derived neurons and functional genomics.