PRDM16 controls a brown fat/skeletal muscle switch. Brown fat increases energy expenditure and protects against obesity through uncoupled respiration. In vivo fate mapping shows brown fat arises from myf5-expressing precursors, not white fat. PRDM16 regulates a bidirectional switch between skeletal myoblasts and brown fat cells. Loss of PRDM16 in brown fat precursors leads to loss of brown fat characteristics and promotes muscle differentiation. Conversely, PRDM16 expression in myoblasts induces brown fat differentiation. PRDM16 activates PPARγ transcriptional function, promoting brown adipogenesis. PRDM16-deficient brown fat shows abnormal morphology, reduced thermogenic gene expression, and elevated muscle-specific gene expression. These findings indicate PRDM16 specifies brown fat lineage from myoblast markers and is not involved in white adipogenesis. PRDM16 binds to PPARγ and coactivates its function, promoting brown fat development. PRDM16-deficient brown fat exhibits dysregulated gene expression, including reduced UCP1 and increased skeletal muscle genes. PRDM16 is essential for brown fat development and thermogenesis. PRDM16 functions in brown fat by coregulating transcription factors and coactivators. PRDM16 deficiency in mice causes death at birth, limiting functional analysis. PRDM16 may be a therapeutic target for obesity treatment by promoting brown fat development. PRDM16 is a key regulator of brown fat cell fate, controlling thermogenesis and mitochondrial biogenesis. PRDM16-deficient brown fat shows reduced thermogenic function and increased muscle gene expression. PRDM16 is required for brown fat development and thermogenesis. PRDM16 regulates brown fat development through PPARγ and PGC-1α. PRDM16 is a critical regulator of brown fat cell fate, controlling thermogenesis and mitochondrial biogenesis. PRDM16 is essential for brown fat development and thermogenesis. PRDM16-deficient brown fat shows reduced thermogenic function and increased muscle gene expression. PRDM16 is required for brown fat development and thermogenesis. PRDM16 regulates brown fat development through PPARγ and PGC-1α. PRDM16 is a critical regulator of brown fat cell fate, controlling thermogenesis and mitochondrial biogenesis.PRDM16 controls a brown fat/skeletal muscle switch. Brown fat increases energy expenditure and protects against obesity through uncoupled respiration. In vivo fate mapping shows brown fat arises from myf5-expressing precursors, not white fat. PRDM16 regulates a bidirectional switch between skeletal myoblasts and brown fat cells. Loss of PRDM16 in brown fat precursors leads to loss of brown fat characteristics and promotes muscle differentiation. Conversely, PRDM16 expression in myoblasts induces brown fat differentiation. PRDM16 activates PPARγ transcriptional function, promoting brown adipogenesis. PRDM16-deficient brown fat shows abnormal morphology, reduced thermogenic gene expression, and elevated muscle-specific gene expression. These findings indicate PRDM16 specifies brown fat lineage from myoblast markers and is not involved in white adipogenesis. PRDM16 binds to PPARγ and coactivates its function, promoting brown fat development. PRDM16-deficient brown fat exhibits dysregulated gene expression, including reduced UCP1 and increased skeletal muscle genes. PRDM16 is essential for brown fat development and thermogenesis. PRDM16 functions in brown fat by coregulating transcription factors and coactivators. PRDM16 deficiency in mice causes death at birth, limiting functional analysis. PRDM16 may be a therapeutic target for obesity treatment by promoting brown fat development. PRDM16 is a key regulator of brown fat cell fate, controlling thermogenesis and mitochondrial biogenesis. PRDM16-deficient brown fat shows reduced thermogenic function and increased muscle gene expression. PRDM16 is required for brown fat development and thermogenesis. PRDM16 regulates brown fat development through PPARγ and PGC-1α. PRDM16 is a critical regulator of brown fat cell fate, controlling thermogenesis and mitochondrial biogenesis. PRDM16 is essential for brown fat development and thermogenesis. PRDM16-deficient brown fat shows reduced thermogenic function and increased muscle gene expression. PRDM16 is required for brown fat development and thermogenesis. PRDM16 regulates brown fat development through PPARγ and PGC-1α. PRDM16 is a critical regulator of brown fat cell fate, controlling thermogenesis and mitochondrial biogenesis.