The Least Understood Placental Galectins: Galectin-14 and Galectin-16 in Human Pregnancy and Placental Biology

Galectins represent a family of proteins which are capable of specifically binding to beta-galactoside-containing sugar molecules, known as glycans. Galectins possess carbohydrate recognition domains (CRDs) that fundamentally determine their ability to bind to sugars. Galectin-14 (Gal-14) and galectin-16 (Gal-16) are members of the galectin family that is particularly associated with the placenta. The galectins in the placenta constitute a specialized subgroup functioning at the maternal–fetal interface. They are expressed primarily in the syncytiotrophoblasts. This trophoblast layer is in direct contact with maternal blood and plays a crucial role in the metabolic, hormonal and immunological interactions between the fetus and the pregnant woman. In order to prepare this structured narrative review, we conducted a structured literature search across the MEDLINE (PubMed), Embase, Cochrane Library and Web of Science Core Collection databases; the final search has been performed on 1 July 2026. The search strategy has combined the terms galectin-14/LGALS14 and galectin-16/LGALS16 with terms related to the placenta, trophoblast, pregnancy, placentation and pregnancy complications. Search results were imported into Mendeley Reference Manager to remove duplicates, and the reference lists of relevant review articles and studies were manually screened. Two reviewers (Z.K. and A.S.) independently screened the titles and abstracts and subsequently evaluated the potentially relevant full-text articles. The final evidence synthesis included primary studies that directly investigated the expression, function, regulation, or clinical associations of LGALS14 or LGALS16; secondary publications were used for background and contextual information. In experimental studies, galectin-14 has been linked to trophoblast migration and invasion—involving mechanisms such as the PI3K/Akt signaling pathway, MMP-9 and N-cadherin—as well as to the modulation of activated maternal immune cell function. Galectin-16 is structurally more distinct and exhibits reduced classical β-galactoside-binding capacity; it appears to be closely associated with trophoblast differentiation and syncytialization, presumably through intracellular protein interactions. Altered expression of placenta-specific galectins has been observed in preeclampsia and fetal growth restriction; however, the causal relationship remains unclear. Clinical evidence regarding their use as biomarkers is emerging at this time; therefore, neither galectin-14 nor galectin-16 can be currently considered as a validated, clinically applicable biomarker. Altogether, available evidence mandates further study of galectin-14 and galectin-16, as they may be important regulators of placental biology and potential biomarker candidates. However, their physiological functions and clinical utility have not yet been sufficiently confirmed; therefore, further prospective and functional studies are required. The strongest putative mechanistic link to the development of preeclampsia exists for galectin-14, primarily involving trophoblast migration and invasion as well as PI3K/Akt-related signaling pathways. In contrast, evidence in connection with the direct role of galectin-16 is limited at present.