In recent years, the highly conserved Lin28 RNA-binding proteins have emerged as factors that define stemness in several tissue lineages. Lin28 proteins repress let-7 microRNAs and influence mRNA translation, thereby regulating the self-renewal of mammalian embryonic stem cells. Subsequent discoveries revealed that Lin28a and Lin28b are also important in organismal growth and metabolism, tissue development, somatic reprogramming, and cancer. In this review, we discuss the Lin28 pathway and its regulation, outline its roles in stem cells, tissue development, and pathogenesis, and examine the ramifications for re-engineering mammalian physiology.
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