The human brain is an intricate and sophisticated organ, composed of interconnected networks of neurons that collaborate to execute specific functions. Disruptions in the generation of specific networks can lead to psychiatric disorders, such as schizophrenia (SCZ), a severe neurological condition with a global prevalence of 1% and a significant genetic basis. Ongoing research indicates that SCZ-related genes influence neuronal differentiation, ultimately resulting in impaired neural circuits. Notably, various studies have identified alterations in sleep spindles as potential inheritable biomarkers for SCZ. Sleep spindles are generated through the interplay of the thalamic reticular nucleus (TRN) with the dorsal thalamus before being relayed to the cortex. Dysregulation of this thalamocortical connectivity is considered central to pathogenetic hypotheses about SCZ. In this context, we generated hiPSC lines from SCZ patients exhibiting a sleep endophenotype. A protocol was developed to mimic TRN ontogenesis, creating an in vitro model to explore the SCZ-related endophenotype. Specifically, we optimized a TRN differentiation protocol using Insulin and CHIR99021 to induce the desired fate. Gene expression analysis confirmed the induced cellular identity by comparing expression patterns with RNA tissue samples from 7 to 20 postconceptional weeks (Human Development Biology Resource - HDBR), resulting in the generation of a reference dataset. This dataset validated the expression profile of TRN neurons derived from hiPSCs. The application of this optimized protocol will facilitate the recapitulation of key stages in human TRN development and differentiation, providing a unique opportunity to closely investigate the sleep endophenotype associated with SCZ in a patient-specific manner.