Mutations in the mouse Tub gene gradually lead to obesity, strongly resembling the late-onset obesity observed in the human population. In addition to excessive deposition of adipose tissue, mice with the Tub phenotype also suffer retinal degeneration and neurosensory hearing loss. A human homolog of the Tub gene has been identified, as have three related proteins, called Tubby-like protein 1 (TULP1), TULP2 and TULP3. When compared to TULP1 and TULP2, TULP3 has a wider tissue expression and is phylogenetically more similar to Tub than either TULP1 or TULP2. TULP1, expressed specifically in the retina, maps to the chromosomal region known to be involved in retinitis pigmentosa, while TULP2 maps within the minimal interval for the rod-cone dystrophy. TULP3 maps to human chromosome 12p13, and shares 69% homology to mouse TULP3. Human RNA from testis, ovary, thyroid and spinal cord contain highly detectable levels of TULP3 transcripts. In the retina, TULP3 is expressed specifically in the inner nuclear layer and ganglion cell layer. TULP1, TULP2 and TULP3 may comprise a unique family of bipartite transcription factors.