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Married couple Jaime (Wendell Ramos), the sole inheritor to the affluent Claveria Group of Companies, and Maita (Glaiza de Castro), having trouble starting their family, hire Lilian (Katrina Halili), daughter of their most trusted house helper, to be their surrogate. Lilian accepts, and later she gives birth to three beautiful girls.
Sisters Raffy and Sam had a perfect relationship until they unintentionally fell in love with the same guy. Raffy recently broke up with her boyfriend, is overprotected to her sister especially when she found that her sister is dating a much older guy, Jake. Raffy will eventually see Jake's value and its the reason why she will fall in love with him.
Jessie’s perfect life becomes a nightmare when her only son, Ethan, is kidnapped by unknown persons. No contact is made by the kidnappers, making the police conclude that the kidnapping was an act of revenge. Jessie has no clue as to who holds a grudge against her or her husband, Brylle, since they live a relatively quiet life. Brylle is a hard-working doctor, while Jessie is a devoted housewife. However, Brylle suspects Amado, the father of a patient he failed to save, and Reign, a lover he is keeping from Jessie.
The relationship between Edward and Belinda will be put to a test after their only daughter, Anna, is kidnapped. With the loss of their real daughter, they will focus their attention and love on their niece, Ariela. While Anna will grow up as Elsa with Aurora. Due to music, their families will cross paths.
Rachel meets Nathan, a gay man who later marries her due to family's pressure. Unhappy and trapped, Nathan plots his fake death and later undergoes to a sexual reassignment and face surgery in another country. Years later, Rachel meets Gavin and falls for him. Gavin has a wife, Venus whom Rachel will eventually find out to be her former husband.
Barangay 143 follows the coming of age story of a young man in search of a father and how he finds an unlikely family in a team of misfits trying to bring glory to their hometown. It's a story about love and family set against the action-packed world of street basketball, where the stakes are always high and life is the biggest game you can win.