C4.4A (Ly6/PLAUR domain-containing protein 3, LYPD3), first reported in 1998, is a tumorigenic and high-glycosylated cell surface protein that has been proven to be linked with the carcinogenic effects in different solid tumors. The elevated expression of LYPD3 is not only demonstrated to be associated with lung adenocarcinoma carcinogenesis and poor prognosis but also there is evidence that LYPD3 can lead to the initiation and development of cancers and the chemoresistance of metastatic cancers by impacting the proliferation and apoptosis of the tumor, which are involved in many important regulatory mechanisms of cancers.