Tyrosinase (TYR) is a multifunctional copper-containing glycoenzyme 
(approximately 80 kDa), which plays a key role in the rate-limiting steps of the 
melanin biosynthetic pathway. This membrane-bound protein, possibly evolved by 
the fusion of two different copper-binding proteins, is mainly expressed in 
epidermal, ocular and follicular melanocytes. In the melanocytes, TYR functions 
as an integrated unit with other TYR-related proteins (TYRP1, TYRP2), 
lysosome-associated membrane protein 1 (LAMP1) and melanocyte-stimulating 
hormone receptors; thus forming a melanogenic complex. Mutations in the TYR gene 
(TYR, 11q14-21, MIM 606933) cause oculocutaneous albinism type 1 (OCA1, MIM 
203100), a developmental disorder having an autosomal recessive mode of 
inheritance. In addition, TYR can act as a modifier locus for primary congenital 
glaucoma (PCG) and it also contributes significantly in the eye developmental 
process. Expression of TYR during neuroblast division helps in later pathfinding 
by retinal ganglion cells from retina to the dorsal lateral geniculate nucleus. 
However, mutation screening of TYR is complicated by the presence of a 
pseudogene-TYR like segment (TYRL, 11p11.2, MIM 191270), sharing approximately 
98% sequence identity with the 3' region of TYR. Thus, in absence of a 
full-proof strategy, any nucleotide variants identified in the 3' region of TYR 
could actually be present in TYRL. Interestingly, despite extensive search, the 
second TYR mutation in 15% of the OCA1 cases remains unidentified. Several 
possible locations of these "uncharacterized mutations" (UCMs) have been 
speculated so far. Based on the structure of TYR gene, its sequence context and 
some experimental evidences, we propose two additional possibilities, which on 
further investigations might shed light on the molecular basis of UCMs in TYR of 
OCA1 patients; (i) partial deletion of the exons 4 and 5 region of TYR that is 
homologous with TYRL and (ii) variations in the polymorphic GA complex repeat 
located between distal and proximal elements of the human TYR promoter that can 
modulate the expression of the gene leading to disease pathogenesis.