RORB, also known as RAR-related orphan receptor B, is a transcription factor that belongs to the nuclear receptor family. It plays crucial roles in cell fate specification, such as in the retina where it is involved in maintaining proper retina layer organization and cone photoreceptor development, and in cortical layer formation. It may also be associated with pathways related to neural circuit formation and homeostasis [8]. Genetic models, like gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable tools for studying RORB's functions.

In mice, loss-of-function mutations in Rorb lead to disorganized retina layers, postnatal degeneration, and immature cone photoreceptor production [8]. A splice-site mutation in rabbits disrupts saltatorial locomotion, reducing RORB-positive neurons in the spinal cord and causing defects in spinal cord interneuron differentiation [7]. In humans, heterozygous variants in RORB are associated with epilepsy and intellectual disability, and in some cases, photosensitive genetic generalized and occipital lobe epilepsy [5,6]. In endometriosis, RORB, along with AEBP1, HOXB6, and KLF2, was identified as a potential biomarker with high diagnostic value [1]. In Alzheimer's disease, RORB is a marker of selectively vulnerable excitatory neurons in the entorhinal cortex, and its variants may decrease the risk of the disease [2,3]. Also, in pancreatic β-cells, RORB is part of the molecular cascade regulating insulin secretion, and its expression is lower in diabetic donors [4].

In conclusion, RORB is essential for multiple biological processes including neural development, locomotion, retinal function, and insulin secretion. Model-based research, especially KO/CKO mouse models, has revealed its significance in diseases such as epilepsy, intellectual disability, Alzheimer's disease, endometriosis, and type 2 diabetes, providing insights into disease mechanisms and potential therapeutic targets.