SYPL1, also known as synaptophysin-like 1, is a neuroendocrine-related tetratransmembrane transport vesicle protein [2,7]. It is involved in vesicle-related pathways, which are crucial for various biological processes. In the context of sperm development, it defines a vesicular pathway essential for sperm cytoplasmic droplet formation, which is important for male fertility [1]. In cancer, it has been associated with tumor-related processes, indicating its overall biological importance in both normal and disease-related biological systems. Genetic models, such as gene knockout mouse models, can be valuable for studying its functions.

Genetic ablation of SYPL1 in mice showed that it dictates the formation and accumulation of saccular elements in the forming cytoplasmic droplet of late spermatids and epididymal sperm. SYPL1 vesicles, derived from the Golgi, are critical for segregating key metabolic enzymes within the cytoplasmic droplet, which are required for sperm development and male fertility [1].

In pancreatic ductal adenocarcinoma (PDAC), gain-of-function and loss-of-function experiments demonstrated that SYPL1 promotes cell proliferation and protects cells from apoptosis. Knockdown of SYPL1 led to sustained extracellular-regulated protein kinase (ERK) activation and cell death, which was related to upregulated reactive oxygen species (ROS) [2].

In colorectal cancer, SYPL1 was upregulated at both mRNA and protein levels. Serum SYPL1 (sSYPL1) was significantly higher in CRC patients compared to controls and adenoma patients, and could distinguish CRC patients from them with high sensitivity and specificity. Fecal SYPL1 (fSYPL1) also showed high performance in distinguishing CRC patients from controls, and its level was positively correlated with tumor-related features. The levels of sSYPL1 and fSYPL1 declined significantly after radical surgery [3,4].

In hepatocellular carcinoma (HCC), SYPL1 overexpression was closely correlated with several malignant clinicopathologic features, and was identified as an independent prognostic factor for overall survival and disease-free survival. It may be associated with epithelial-mesenchymal transition (EMT) of HCC cells [5].

In oral squamous cell carcinoma (OSCC), YY1 promotes OSCC cell progression via up-regulating Kcnq1ot1 to sponge miR-506-3p and elevate SYPL1 [6].

In glioblastomas, SYPL1 was found to be upregulated in PRNPhigh/PRNP + cells, and vesicular dynamics signatures were strongly correlated with PRNP/PrPC levels where SYPL1 is involved [8].

In a study on JNK1/JNK3 interactome, SYPL1 was identified as a typical JBD-dependent interactor shared by JNK1α1 and JNK3α1 [9].

In conclusion, SYPL1 plays essential roles in multiple biological processes. In male fertility, it is crucial for sperm cytoplasmic droplet formation. In various cancers including PDAC, CRC, HCC, and OSCC, it is involved in processes such as cell proliferation, apoptosis, and metastasis, influencing cancer prognosis. The study of SYPL1 using gene knockout mouse models and other functional experiments has provided important insights into these functions, which may help in understanding the mechanisms of related diseases and developing potential therapeutic strategies.