LHX4 is a LIM-homeodomain transcription factor that functions as a sequence-specific DNA-binding protein with preferential binding to methylated CpG sequences 1. The gene encodes six exons located on chromosome 1.1-1q24.3 2 and plays critical roles in pituitary gland development and nervous system formation, particularly in motor neuron development 2. LHX4 demonstrates CNS-specific expression, with abundant expression in the cerebral cortex and spinal cord motor neurons 2. As a regulatory transcription factor, LHX4 functions alongside LHX3 in establishing specialized hormone-secreting cells of the anterior pituitary 34. Mutations in LHX4 cause combined pituitary hormone deficiency (CPHD), characterized by growth hormone deficiency, reproductive system deficits, and metabolic disorders 3. While LHX4 mutations are rare in CPHD, they represent clinically significant genetic causes, with documented pathogenic variants identified in patient cohorts 5. Clinical manifestations include short stature, empty sella syndrome, and in rare cases, congenital myopathy 6. Growth hormone replacement therapy effectively addresses the short stature phenotype 3. LHX4 may interact with other developmental genes such as NR5A1 during pituitary and gonadal development 7.