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Anti-melanogenic agents currently available to treat skin hyperpigmentation reportedly show various side effects. Therefore, new strategies are needed. Human milk oligosaccharides, such as 2'-fucosyllactose (2'-FL), have therapeutic activity with low cytotoxicity. 2'-FL leads to the formation of LC3B/PMEL double-positive autophagosomes via activation of the AMPK?ULK1 signaling axis. Detection of LC3B/PMEL co-localization may allow assessment in detail of the melanin production/degradation balance, thereby identifying potential anti-melanogenic agents. Taken together, 2'-FL may represent a non-toxic agent for preventing skin hyperpigmentation.