A splice odyssey: periostin’s journey through the sea of crabs

Periostin is an extracellular matrix protein involved in processes ranging from early embryonic development to life-threatening cancer progression. Instead of acting as a single entity, it exists in numerous alternatively spliced isoforms, primarily differing in their C-terminal region, which drives diversification and context-dependence in its biological functions. Despite growing interest, inconsistencies in nomenclature and fragmented data still complicate the interpretation of isoform-specific roles. Therefore, the aim of this review is to provide a structured overview of periostin isoforms, focusing on their roles in development and carcinogenesis, while addressing challenges in their nomenclature. During embryogenesis, expression of periostin is dynamically regulated across developmental stages and tissues. Distinct isoforms exhibit specific patterns, both spatially and temporally, that reflect specialized functions during organogenesis (particularly in the cardiac, neural, and skeletal systems), and as experimental evidence points out, certain exons play critical roles in morphogenesis. Regulatory mechanisms influencing these patterns persist beyond development and are often changed in pathological conditions. In oncological diseases, expression of periostin isoforms varies widely between tumor types and microenvironments. Many isoforms are present in malignant as well as in adjacent non-malignant tissues, with differences in their relative abundance. Functionally, exon 17-containing variants tend to influence tumor cell-intrinsic properties, while variants with exon 21 are more closely linked to stromal interactions and modulation of the tumor microenvironment. Interesting is also the fact that periostin can exert both tumor-promoting and tumor-limiting effects, depending on the isoform and biological context. Taken together, periostin isoforms represent a complex regulatory system whose better understanding and standardized classification may enhance their potential in diagnostics and therapy.