Insulin-like growth factor-1 (IGF-1) is a multipotent growth factor involved in the growth, development and regulation of homeostasis in a tissue-specific manner. Alternative splicing, multiple transcription initiation sites and different polyadelynation signals give rise to diverse mRNA isoforms, such as IGF-1Ea, IGF-1Eb and IGF-1Ec transcripts. There is increasing interest in the expression of the IGF-1 isoforms and their potential distinct biological role. IGF-1Ec results from alternative splicing of exons 4-5-6 and its expression is upregulated in various conditions and pathologies. Recent studies have shown that IGF-1Ec is preferentially increased after injury in skeletal muscle during post-infarctal myocardium remodelling and in cancer tissues and cell lines. A synthetic analogue corresponding to the last 24 aa of the E domain of the IGF-1Ec isoform has been used to elucidate its potential biological role. The aim of the present review is to describe and discuss the putative bioactivity of the E domain of the IGF-1Ec isoform.