{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTyrosinase‐related protein 1 (TYRP1) is a melanocyte‐specific protein central to the melanogenic machinery responsible for eumelanin synthesis. It functions both as a catalytic enzyme—oxidizing melanin precursors such as 5,6‐dihydroxyindole‐2‐carboxylic acid—and as a modulator of tyrosinase (TYR) stability and activity, thereby contributing to proper folding, processing, and trafficking of melanogenic enzymes. TYRP1 also plays a structural role in melanosome maturation, influencing pigment‐containing organelle ultrastructure and melanocyte survival. Its biochemical properties, including metal cofactor requirements and complex formation with TYR, have been characterized to reveal how intrinsic protein–protein interactions (and even temperature‐dependent oligomerization) may protect these enzymes from degradation and modulate their catalytic function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have long documented that variants in TYRP1 contribute to the wide spectrum of human pigmentary phenotypes—including differences in hair, skin, and eye color—and modulate risks for pigment‐related disorders. Missense mutations and other allelic variants in TYRP1 have been implicated in oculocutaneous albinism type 3 (OCA3), a disorder characterized by reduced melanin synthesis, as well as in subtler variations such as blond hair in certain populations. Moreover, aberrant TYRP1 expression and non‑canonical functions of its mRNA—such as sequestering tumor‐suppressive microRNAs like miR‑16—have been associated with melanoma progression and poorer clinical outcomes. These observations, together with association studies linking TYRP1 genetic variants to melanoma risk and pigmentary traits, underscore its dual role in normal pigmentation and disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTYRP1 expression is tightly controlled by transcriptional networks—most notably by MITF—and by regulatory elements located in both proximal and distal regions of its gene. In addition to transcriptional regulation, perturbations in TYRP1 mRNA levels can influence cell fate via microRNA interactions, thereby affecting melanoma progression, immune recognition, and even responses to ultraviolet radiation in conditions such as vitiligo. Advanced proteomic and biochemical studies have illuminated how interacting partners (for example, GIPC) and post‑transcriptional mechanisms modulate TYRP1 function, further emphasizing its value as a biomarker for melanoma prognosis and a potential therapeutic target in pigmentary disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "42"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hidenori Watabe, Julio C Valencia, Ken-Ichi Yasumoto, et al. 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