Abstract
The scarcity of robust models and therapeutic options for rare diseases continues to hamper their preclinical investigation. Traditional animal models and two-dimensional cell cultures are limited in their ability to replicate human heredity-associated traits and complex pathological features. Organoids-on-a-chip approaches open up new frontiers in rare-disease research via the integration of organ chips and organoid technology. This integrative strategy offers immense opportunities for the mimicry of disease-related traits, the clarification of the mechanisms underlying disease, and the prediction of treatment responses in a highly human-related manner. This forward-looking perspective suggests organoids on chips are transformative tools for parsing rare-disease pathogenesis, accelerating therapeutic discovery, and bridging the gap between basic research and precision medicine.