“…One alternative to the matrix-mediated hypothesis is the cell-mediated hypothesis, which proposes that crystal nucleation occurs in hemocytes or OME, and that crystal-bearing cells transport nascent crystals intracellularly to the mineralization front (Mount et al, 2004;Gong et al, 2008a;Xiang et al, 2014). Although the cellular basis has been reported in many other biomineralization, such as osteoclasts and primary mesenchyme cells involved in bone and spicule formation in vertebrates and echinoderms, respectively (Wilt, 2002;Kylmaoja et al, 2016), this hypothesis still largely scraps the dominant paradigm in molluscan biomineralization, and has been supported by increasing evidence, which will be introduced in the following text (Mount et al, 2004;Fleury et al, 2008;Johnstone et al, 2008Johnstone et al, , 2015Kong et al, 2015;Li et al, 2016). To date, cells coming from two different sources have been observed involved in shell formation: (1) OMEs mediate shell formation by either directly involving in the nucleation and remodeling process of CaCO 3 mineral (Kong et al, 2015) or secreting the organic matrix, among which shell matrix proteins (SMPs) regulate the diversity of shell shapes by orchestrating the CaCO 3 crystals in a specific manner (Lowenstam and Weiner, 1989;Zhang and Zhang, 2006;Marin et al, 2008;Ivanina et al, 2017); and (2) hemocytes participate in the deposition of intracellular CaCO 3 crystals and deliver them to the mineralization site (Mount et al, 2004;Fleury et al, 2008;Kádár, 2008;Mount and Pickering, 2009;Johnstone et al, 2015;Li et al, 2016;Ivanina et al, 2017).…”