This alternative splicing of the 39 exons generates coding sequences for a secreted MAEBL isoform in addition to the transmembrane MAEBL isoform. The two main isoforms of MAEBL are referred to as ORF1 and ORF2. The ORF1 product is structurally homologous to the Duffy binding-like erythrocyte binding protein ligands. ORF2 is a putative soluble isoform that has an alternative carboxyl terminus without a transmembrane domain and its accompanying cytoplasmic domain. ORF1 and ORF2 are differentially expressed in midgut and salivary gland sporozoites and MAEBL expression was best correlated with the appearance of the canonical ORF1 transmembrane transcript. Because of this complexity in expression it is not clear what isoform of MAEBL is functionally important in mature sporozoites for invasion of the salivary glands. Either MAEBL serves simply as an adhesin to mediate sporozoite attachment to the salivary glands or the C-terminal portion of MAEBL also has a role to interact with cytoplasmic elements to mediate its function during invasion. By studying the role of the different forms of MAEBL it is possible to understand better the biology of the Plasmodium sporozoite and, as a result, generate information useful for the development of tools such as a transmission blocking vaccine to stop the parasite passage in the vector. Here we show that a transmembrane form of P. falciparum MAEBL is essential for the invasion of the Anopheles salivary glands. Sporozoite invasion of the anopheline salivary gland is critical for malaria parasite transmission and yet it is one of the most poorly studied stages of this deadly pathogen. Similarly, MAEBL ligand domains and AMA1 ectodomain sequence and structure analysis comparison suggests a role in similar steps in the invasion of host cells. This would place the function of MAEBL before TRAP involvement during the sporozoite invasion process into salivary glands. Therefore, we conclude that we do not see sporozoites attached to the salivary glands for the MAEBL deficient mutants, because similar to merozoite��s initial attachment the sporozoite attachment to salivary glands is an unstable and reversible step when invasion does not proceed to junction formation.